"Hereditary nephritis" denominates a heterogeneous group of diseases. We are studying the biochemical nature of hereditary nephritis that is characterized by hematuria, by progressive ultrastructural defects of glomeruli, by apparent absence of immunologically mediated glomerular damage, by X-linked dominant inheritance, and by high and low incidence of renal failure in affected males and females, respectively (Ann. Int. Med. 88, 176-182, 1978; Path. Res. Pract. 168, 146-162, 1980). Some of our families have the classical Alport syndrome of associated sensorineural deafness and hereditary nephritis. We found an unusual protein of molecular weight ca. 180,000 in urines of a majority of tested patients with hereditary nephritis of Alport syndrome. This protein was not found in urines of patients with a variety of other kidney diseases, except from a minority of patients with membranous nephropathy or membranonoproliferative glomerulonephritis. We tentatively identified the protein from hereditary nephritis patients' urines as proteolytically degraded form of the third component of complement. We seek to define the structure and origin of the urine protein and to determine if these represent or are primary consequences of the basic biochemical defect in this disease. We hypothesize that a defect of terminal stages of complement metabolism in the blood plasma leads to saturation of glomerular complement receptors with hemolytically inactive C3-catabolite that is not readily detectable by the usual immunofluorescence studies. We further hypothesize that saturation of the kidney complement receptors perturbs metabolism of glomerular basement membrane.